Formulation development of itraconazole PEGylated nano-lipid carriers for pulmonary aspergillosis using hot-melt extrusion technology

Gauri Shadambikar; Sushrut Marathe; Nan Ji; Mashan Almutairi; Suresh Bandari; Feng Zhang; Mahavir Chougule; Michael Repka

doi:10.1016/j.ijpx.2021.100074

Formulation development of itraconazole PEGylated nano-lipid carriers for pulmonary aspergillosis using hot-melt extrusion technology

Int J Pharm X. 2021 Mar 3:3:100074. doi: 10.1016/j.ijpx.2021.100074. eCollection 2021 Dec.

Authors

Gauri Shadambikar¹, Sushrut Marathe¹, Nan Ji¹, Mashan Almutairi^{1

2}, Suresh Bandari¹, Feng Zhang³, Mahavir Chougule¹, Michael Repka^{1

4}

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, MS 38677, USA.
² Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia.
³ College of Pharmacy, The University of Texas at Austin, TX 78712, USA.
⁴ Pii Center for Pharmaceutical Technology, University of Mississippi, University, MS 38677, USA.

Abstract

Pulmonary delivery is a promising alternative for the oral treatment of pulmonary aspergillosis. This study aimed to develop continuous and scalable itraconazole PEGylated nano-lipid carriers (ITZ-PEG-NLC) for inhalation delivery. The feasibility of preparing NLCs utilizing hot-melt extrusion (HME) coupled with probe sonication was investigated. The process parameters for HME and sonication were varied to optimize the formulation. ITZ-PEG-NLC (particle size, 101.20 ± 1.69 nm; polydispersity index, 0.26 ± 0.01) was successfully formulated. The drug entrapment efficiency of ITZ-PEG-NLC was 97.28 ± 0.50%. Transmission electron microscopy was used to characterize the shape of the particles. The developed formulations were evaluated for their aerodynamic properties for pulmonary delivery. The lung deposition of ITZ-PEG-NLC was determined using an Anderson Cascade Impactor and Philips Respironics Sami the Seal Nebulizer Compressor. In vitro cytotoxicity studies were performed using A549 cells. A burst-release pattern was observed in ITZ-PEG-NLC with a drug release of 41.74 ± 1.49% in 60 min. The in vitro aerosolization of the ITZ-PEG-NLC formulation showed a mass median aerodynamic diameter of 3.51 ± 0.28 μm and a geometric standard deviation of 2.44 ± 0.49. These findings indicate that HME technology could be used for the production of continuous scalable ITZ-PEG-NLC.

Keywords: Hot-melt extrusion; Inhalation; Itraconazole; Nanostructured lipid carriers; PEGylation; Pulmonary drug delivery.